Systemic therapy decisions across breast cancer

By Agata Buczak

​​​​Systemic treatment decisions are increasingly guided by disease subtype, stage, and evolving therapeutic options​

Systemic therapy choices across early and metastatic breast cancer increasingly depend on disease subtype, stage, and emerging evidence that guides escalation and de‑escalation of treatment. In collaboration with the Bulgarian Joint Cancer Network (BJCN), insights from the San Antonio Breast Cancer Symposium (SABCS) 2025, presented at the licensed Best of SABCS^® 2025 meeting in Bulgaria, highlight how recent clinical trials are refining practice across early and metastatic disease.

Why is tamoxifen not recommended as an alternative to surgery in low-risk ER-positive DCIS?

In the LORETTA trial, Hiroji Iwata et al. investigated whether endocrine therapy could replace surgery in patients with small, low‑risk, grade 1–2 estrogen receptor (ER)‑positive ductal carcinoma in situ without comedonecrosis (<2.0 cm by imaging)^.1

At 5 years, tamoxifen (20 mg daily) was associated with a higher cumulative incidence of invasive breast cancer compared with surgery.¹ Although surgery‑free survival for ipsilateral or contralateral invasive disease and overall survival were similar between groups, surgery provided superior invasive disease risk reduction.¹

What is the role of carboplatin in early triple-negative breast cancer planned for neoadjuvant therapy, regardless of germline BRCA1/2 status?

For early triple‑negative breast cancer (TNBC) selected for neoadjuvant systemic therapy, evidence supports adding carboplatin irrespective of pathogenic germline BRCA1/2 mutation status.²

In a pooled analysis of BrighTNess, CALGB 40603 (Alliance), and GeparSixto, Brooke Felsheim et al. reported a significant improvement in event‑free survival with carboplatin addition, despite no consistent improvement in pathological complete response or overall survival.² These findings highlight a dissociation between early response metrics and longer‑term outcomes.

What is the role of adjuvant giredestrant compared with standard endocrine therapy in early luminal HER2-negative breast cancer? 

In the phase 3 lidERA trial, Aditya Bardia et al. compared adjuvant giredestrant with standard endocrine therapy (aromatase inhibitor or tamoxifen) in early luminal human epidermal growth factor receptor 2 (HER2)‑negative breast cancer.³

At 3 years, giredestrant significantly improved invasive disease‑free survival, with fewer invasive recurrences and reduced distant dissemination than standard therapy.³

How do antibody–drug conjugates inform regimen selection in neoadjuvant HER2-positive treatment?

In the I‑SPY 2.2 trial, Paula Pohlmann et al. showed that neoadjuvant ARX788 significantly increased pathologic complete response (pCR) rates and the proportion of patients achieving residual cancer burden 0/I compared with sequential taxane‑ and anthracycline‑based regimens.⁴

Similarly, in DESTINY‑Breast 11, Giuseppe Curigliano et al. reported that neoadjuvant trastuzumab deruxtecan, given alone or followed by paclitaxel plus dual HER2 blockade, achieved pCR rates and safety outcomes comparable with dose‑dense anthracycline‑based regimens.⁵

How do endocrine-based strategies inform decision-making in advanced luminal HER2-negative metastatic disease?

In the AMBRE study, Véronique Diéras et al. reported that first‑line abemaciclib plus endocrine therapy improved progression‑free survival compared with chemotherapy, including in symptomatic or high‑volume disease.⁶

Moreover, in SERENA‑6, François-Clément Bidard et al. showed that early detection of ESR1 mutations using circulating tumor DNA and switching from aromatase inhibitor to camizestrant before clinical progression significantly prolonged progression‑free survival.⁷

Key takeaways

• Surgery remains preferred over tamoxifen to reduce invasive risk in low‑risk ER-positive DCIS
• Carboplatin improves long‑term outcomes in early TNBC despite limited impact on pCR
• Adjuvant endocrine options in luminal HER2‑negative disease continue to expand
• Antibody–drug conjugates are reshaping neoadjuvant treatment selection in HER2-positive breast cancer
• Endocrine‑based strategies remain central in advanced luminal HER2‑negative disease, supported by molecular monitoring

Read more about consensus and new recommendations from Best of 2025 SABCS^® Bulgaria.